Attention deficit-hyperactivity disorder (ADHD), among the most common disorders of childhood, is characterized by the inability to marshal and sustain attention, modulate activity level, and moderate impulsive actions. Difficulties are evident at home, where ADHD children often have a hard time following rules, often create disturbances at mealtime, bedtime, or on family outings, are in frequent conflict with siblings, and rarely complete homework without a struggle or in the absence of parental supervision. In the classroom, ADHD children often stand out because of their lack of concentration, failure to follow class routines, fidgetiness, inappropriate verbalizations and disruptiveness, and difficulty working independently. Such maladaptive behaviors are inconsistent with age and developmental level. Evidence of symptoms is obtained directly from the child, the parents and the teachers. The prevalence of ADHD is estimated at 3 to 7% of all children, and ADHD is a chronic condition with symptoms experienced over a lifetime.
Many drug therapies use immediate-release oral dosage forms administered at spaced intervals to provide and maintain a desired therapeutic effect over a prolonged therapy period.
For example, drugs used in treating Attention Deficit Disorder (ADD) and ADHD such as ADDERALL® and RITALIN® are administered two or three times a day. For various reasons, subjects often experience difficulty complying with this administration schedule. Conventional ADHD compositions such as ADDERALL® XR and METADATE® CD are only available in solid dosage forms for swallowing. Many people, especially children, have difficulty swallowing such standard solid dosage forms.
Amphetamines are non-catecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures, and weak bronchodilator, and respiratory stimulant action. The racemic form of amphetamine in EVEKEO® differs from dextroamphetamine as in DEXEDRINE® or DEXAMPEX or the mixed amphetamine salts in Adderall® as only 25% of the dose in EVEKEO® is in the form of the l-isomer. The 1-isomer is more potent than the d-isomer in cardiovascular activity, but much less potent in causing CNS excitatory effects. The racemic mixture of EVEKEO® is also is less effective as an appetite suppressant when compared to dextroamphetamine.
EVEKEO® tablets containing racemic amphetamine sulfate, available in 5 and 10 mg dose strengths, are typically administered starting with the lowest dose, and the dosage may be individually adjusted for each patient. EVEKEO® is not recommended for children under 3 years of age. In children from 3 to 5 years of age, the initial dose is typically 2.5 mg daily; the daily dosage may be raised in increments of 2.5 mg at weekly intervals until the optimal response is obtained. In children 6 years of age or older, the starting dose is typically 5 mg once or twice daily; the daily dosage may be raised up to a maximum total daily dose of 40 mg in increments of 5 mg at weekly intervals until the optimal response is obtained. With tablets, the first dose is typically administered upon awakening, and additional doses (1 to 2) may be administered at intervals of 4 to 6 hours. Many pediatric patients experience difficulty in swallowing tablets and capsules, and many parents and care givers find it hard to ensure that young ADHD children swallowed their CNS stimulants without “cheeking”. The availability of pleasant tasting orally disintegrating tablets which rapidly disintegrate on contact with saliva into a viscous, easy-to-swallow suspension would minimize, if not eliminate, these problems, and improve compliance.
U.S. Pat. No. 8,709,491 assigned to Neos Therapeutics is directed to easily ingested, once-daily oral compositions, including liquid drug suspensions, chewable compositions, and orally disintegrating compositions, which can be easily administered with or without water. These dosage forms, especially ODTs consist of two types of particles—uncoated resinate particles and resinate particles coated with a delayed or controlled release coating can provide an effective treatment over a prolonged period of time. However, ODT dosage forms favored by individuals who have difficulty swallowing conventional solid dosage forms (e.g., children or individuals with dysphagia), apart from being in the extended release form, contain a combination of 4 different salt forms with a dextro to levo isomer weight ratio of 3:1, and hence, are not substitutable for EVEKEO®.